Relexxii

(methylphenidate hydrochloride extended-release, OROS)
Relexxii (methylphenidate hydrochloride extended-release, OROS); CII
Full Prescribing Information
DailyMed Drug Information
Summary
Relexxii is a long-acting methylphenidate tablet using the same class of OROS osmotic delivery as Concerta, approved for ADHD from age 6 through 65. Its differentiator is the strength ladder: 45 mg, 63 mg and 72 mg exist as single tablets, so a patient needing more than 54 mg takes one tablet rather than two. It is not labeled as bioequivalent to Concerta. Schedule II; brand and authorized generic.
Forms & Strengths
Extended-release tablets (OROS, swallow whole): 18 mg, 27 mg, 36 mg, 45 mg, 54 mg, 63 mg, 72 mg
Dosing
Age: 6 to 65 y/o
Onset: ~ 1 hour
Duration: up to 12 hours
Release Profile: 18% IR / 82% ER via OROS osmotic delivery
Initial Dose:
6 to 17 y/o, new to methylphenidate: 18 mg once daily in the morning
18 to 65 y/o, new to methylphenidate: 18 mg or 36 mg once daily in the morning
From methylphenidate 2-3 times daily, per dose: 5 mg to 18 mg; 10 mg to 36 mg; 15 mg to 54 mg; 20 mg to 72 mg
Titration: 18 mg every 7 days; 27, 45 and 63 mg give intermediate steps
Max Dose:
6 to 12 y/o: 54 mg/day
13 to 17 y/o: 72 mg/day, not to exceed 2 mg/kg/day
18 to 65 y/o: 72 mg/day
Considerations: Swallow whole; chewing or dividing destroys the osmotic pump. The 45, 63 and 72 mg strengths avoid two-tablet regimens above 54 mg. Do not substitute milligram-for-milligram with another methylphenidate.
Pharmacology
Mechanism: Blocks presynaptic dopamine and norepinephrine reuptake at DAT and NET; does not meaningfully promote catecholamine release at therapeutic doses
Delivery / Release: 18% IR / 82% ER via OROS osmotic delivery. The overcoat dissolves within an hour, then a push layer forces drug through a laser-drilled orifice; two core layers make release rise over 6 to 7 hours.
Metabolism: De-esterified to PPAA (ritalinic acid), inactive. Half-life ~3.5 hours, ~90% recovered in urine. Renal impairment has little effect.
Class Positioning: Same osmotic principle as Concerta, not the same product: 18% against 22% immediate fraction, Tmax 5.5 h against 6 to 10 h, no bioequivalence study. Advantage: single-tablet dosing at 45, 63 and 72 mg.
Indications
ADHD (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6 to 65 y/o
Off-Label Uses
ADHD in children 4 to 5 years old (ICD-10: F90.x): behavioral parent training first line; if medication is needed use IR methylphenidate, not OROS. Expert consensus. (AAP 2019)
Narcolepsy (ICD-10: G47.419): IR methylphenidate carries this indication, Relexxii does not. Insufficient.
Substituting for Concerta at the same strength: common at 18 to 54 mg but unsupported by any bioequivalence study. Recheck response after a switch. Insufficient.
Where the evidence does not support use: treatment-resistant depression, binge eating disorder, cancer-related and chronic fatigue. Adult literature only; insufficient in children. (AHRQ 2024)
Cognitive enhancement in a youth without ADHD: not an indication and not supported.
Contraindications & Warnings
Boxed Warning: Abuse, misuse and addiction, with overdose and death. Assess abuse risk before prescribing and reassess throughout treatment.
Contraindicated:
Hypersensitivity to methylphenidate; angioedema and anaphylaxis reported
MAOI use, current or within 14 days: hypertensive crisis
Use with caution:
Structural cardiac abnormality, cardiomyopathy, arrhythmia or coronary disease: avoid
Pre-existing hypertension: monitor blood pressure and pulse
Psychotic or bipolar disorder: exacerbation and treatment-emergent mania
GI narrowing: the tablet is nondeformable
Significant hyperopia or angle-closure risk: refer to ophthalmology
Personal or family history of tics or Tourette's syndrome
Substance use disorder in the patient or the household
Screen before starting:
Cardiac history and exam including family sudden death; the label requires no routine ECG
Tics, and risk factors for a manic episode
Abuse and diversion risk in patient and household
Ability to swallow a tablet whole; any GI stricture or bowel surgery
Baseline height, weight, blood pressure and heart rate
Drug Interactions
MAOIs (phenelzine, tranylcypromine, selegiline, linezolid, methylene blue): hypertensive crisis. Contraindicated within 14 days.
Antihypertensives: effectiveness reduced. Increase BP monitoring and adjust the antihypertensive.
Halogenated anesthetics (sevoflurane, isoflurane, desflurane): intraoperative BP and HR surge. Hold on the day of surgery.
Risperidone: EPS may increase when either dose changes in either direction. Monitor across any titration.
Serotonergic agents (SSRIs, SNRIs, TCAs, triptans, tramadol): serotonin syndrome in postmarketing reports only, not in the interaction table. Counsel on symptoms.
Administration
Once daily in the morning, with or without food.
Swallow whole. Do not chew, divide or crush; there is no sprinkle option.
If the child cannot swallow a tablet, use a bead capsule (Ritalin LA) or a liquid (Quillivant XR).
The intact shell passes in the stool; warn the family before the first dose.
Never substitute milligram-for-milligram; use the labeled conversion table and recheck response after any switch.
Missed dose: skip it rather than giving it late in the day.
Store locked; the 63 and 72 mg strengths are high-value diversion targets.
Side Effects
Common, pediatric 6 to 17 y: upper abdominal pain, the only reaction above 5%; insomnia, nasopharyngitis, vomiting, pyrexia 2% to 3%.
Common, adults (all above 5%): decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight loss, irritability, hyperhidrosis.
Serious:
Sudden death with structural cardiac disease: avoid the drug in that population
New psychosis or mania, including with no psychiatric history: consider discontinuing
Priapism, sometimes surgical, typically after a dose increase and also during drug holidays
Peripheral vasculopathy and Raynaud's with digital ulceration: assess digits each visit
Long-term growth suppression; GI obstruction from the nondeformable tablet in pre-existing narrowing
Acute angle closure glaucoma; new or worsening tics and Tourette's
Postmarketing: convulsion, dyskinesia, serotonin syndrome, hypersensitivity reactions
Monitoring & Labs
Cardiovascular: BP and HR at baseline, at every dose change, and at least every 6 months.
Growth: height, weight and BMI at baseline and every 6 months; failure to gain triggers interruption.
Appetite and sleep: at every visit and dose change; the usual reasons titration stalls short of 72 mg.
Psychiatric and tics: screen for psychosis, mania, aggression, depressed mood and tics at baseline and every visit.
Abuse and diversion: at every refill, pill count, ask about sharing and selling, check the PDMP. A boxed-warning obligation.
Dose ceiling: at every titration step in a 13 to 17 year old, recalculate 2 mg/kg/day. Under 36 kg the weight cap bites before the 72 mg cap.
Laboratory: none is required by this label.
Discontinuation & Taper
No taper required; the label gives no tapering schedule.
Discontinue if no improvement after appropriate dose adjustment over one month.
Withdrawal after prolonged use: dysphoria, fatigue, vivid dreams, sleep change, increased appetite.
Priapism has occurred during drug holidays and on discontinuation.
Drug holidays are reasonable where growth or appetite limits treatment; an interrupted day is fully unmedicated.
Pregnancy & Lactation
Pregnancy: no drug-associated risk of major birth defects or miscarriage identified. Stimulant vasoconstriction may reduce placental perfusion. Background risk 2% to 4% and 15% to 20%. Weigh against untreated maternal ADHD.
Lactation: infant dose 0.16% to 0.7% of the maternal weight-adjusted dose; undetectable in infant serum in every reported case, including 72 mg daily. Not a reason to stop breastfeeding. (LactMed 2025)
Lactation, milk supply: prolactin falls; large doses may interfere before supply is established. Monitor the infant for agitation, anorexia and poor weight gain. (LactMed 2025)
Exposure Registry: National Pregnancy Registry for ADHD Medications, 1-866-961-2388.
Counseling Points
Counsel the family on:
Relexxii and Concerta not being the same tablet even where milligrams match; watch the first week after a substitution.
The 45, 63 and 72 mg strengths being the reason for this product: one tablet replaces two.
Seeing the intact shell in the stool; it is the spent pump, not a wasted dose.
Half a 45 mg tablet being a broken osmotic pump, not 22.5 mg.
Dosing at the same early hour daily; a late dose pushes the ascending peak into the evening.
Moving the largest meal to breakfast and the evening, when appetite returns.
Locked storage; the high strengths are the ones peers ask for.
Advise them to call for:
Chest pain, fainting, or a racing heart that does not settle.
New hallucinations, or new suspicious or fearful thinking.
Numbness, coldness or colour change in fingers or toes.
A new or markedly worse tic.
A painful erection lasting more than a few hours; a surgical emergency.
Severe abdominal pain or vomiting, especially with any history of bowel narrowing.
Eye pain with blurred vision or halos around lights.
Clothes fitting more loosely, or no weight gain across a few months.
References
DailyMed. Relexxii (methylphenidate hydrochloride) extended-release tablets prescribing information. Vertical Pharmaceuticals. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=22d5fa47-b5b9-4fd9-980c-4eb88e95ae5d
DailyMed. Concerta (methylphenidate hydrochloride) extended-release tablets prescribing information. Janssen Pharmaceuticals. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a88218c-5b18-4220-8f56-526de1a276cd
FDA. openFDA National Drug Code Directory, generic_name methylphenidate. 2026. https://api.fda.gov/drug/ndc.json?search=generic_name:%22methylphenidate%22&limit=1000
LactMed. Methylphenidate. Drugs and Lactation Database, NICHD. 2025. https://www.ncbi.nlm.nih.gov/books/NBK501310/
American Academy of Pediatrics. Clinical practice guideline for the diagnosis, evaluation, and treatment of ADHD in children and adolescents. Pediatrics. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/
AHRQ. Attention deficit hyperactivity disorder: diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK602989/